The design of aircraft hydraulic pipeline system is limited by many factors, such as the integrity of aviation structure or narrow installation space, so the limited clamp support position should be considered. This paper studied the frequency adjustment and dynamic responses reduction of the multi-support pipeline system through experiment and numerical simulation. To avoid the resonance of pipeline system, we proposed two different optimization programs, one was to avoid aero-engine working range, and another was to avoid aircraft hydraulic pump pulsation range. An optimization method was introduced in this paper to obtain the optimal clamp position. The experiments were introduced to validate the optimization results, and the theoretical optimization results can agree well with the test. With regard to avoiding the aero-engine vibration frequency, the test results revealed that the first natural frequency was far from the aero-engine vibration frequency. And the dynamic frequency sweep results showed that no resonance occurred on the pipeline in the engine vibration frequency range after optimization. Additionally, with regard to avoiding the pump vibration frequency, the test results revealed that natural frequencies have been adjusted and far from the pump vibration frequency. And the dynamic frequency sweep results showed that pipeline under optimal clamp position cannot lead to resonance. The sensitivity analysis results revealed the changing relationships between different clamp position and natural frequency. This study can provide helpful guidance on the analysis and design of practical aircraft pipeline.